The ability of a Colletotrichum sp., originally isolated from Brassica campestris, to infect Arabidopsis thaliana was examined. Sequence analysis of the internal transcribed spacer (ITS)1, 5.8S RNA gene and ITS2 regions of ribosomal (r)DNA showed the pathogen to be Colletotrichum destructivum. The host range was broad, including many cruciferous plants and some legumes. At 25 degrees C, all A. thaliana accessions tested were susceptible to the Brassica isolates of C. destructivum; however, at 15 degrees C, the accession Ws-2 showed a temperature-dependant resistance, in which single epidermal cells underwent a rapid hypersensitive response. Legume isolates of C. destructivum were unable to infect A. thaliana and induced deposition of callose papillae at sites of attempted penetration. In compatible interactions, C. destructivum showed a two-stage, hemibiotrophic infection process. The initial biotrophic phase was associated with large, intracellular primary hyphae and was confined to one epidermal cell; whereas, in the subsequent necrotrophic phase, narrow secondary hyphae extensively colonized the tissue and conidia were produced in acervuli. An efficient transformation system was established for C. destructivum, using Agrobacterium-mediated transfer of DNA. The ability to genetically manipulate both partners in the interaction is an important advantage, and the Arabidopsis-Colletotrichum pathosystem should provide a valuable new model for dissecting plant-fungal interactions.

Sequence analyses have revealed the existence of homology between certain aeroallergens and proteolytic enzymes. This homology can be expressed functionally, but its significance to airway pathophysiology is unknown. Studies with Madin-Darby canine kidney cells and canine tracheal epithelial cells grown on plastic substrata or matrix proteins suggest that Der p1, a major allergen from the house dust mite Dermatophagoides pteronyssinus and a cysteine proteinase, or the unfractionated growth medium extract (SGME) from which it was purified, are both capable of causing cell detachment. The ability of both agents to produce functional changes in the barrier function of the epithelium was further demonstrated using isolated bovine airway preparations. Over a 3-h duration, both Der p1 and SGME elicited significant increases in the permeability of isolated sheets of bronchial mucosa to serum albumin. Exposure of isolated bronchial segments to luminally applied solutions of Der p1 resulted in histologic evidence of epithelial injury. Neither Der p1 nor SGME was active in these experimental systems unless chemically reduced, suggesting that the effect was initiated by cysteine proteinase activity. Similar augmentation of mucosal permeability and tissue injury was produced by bovine trypsin and collagenase from Clostridium histolyticum. In both the isolated mucosal sheet model and in cultured cells, the actions of Der p1 or SGME were associated with relatively little cytolysis, suggesting a specific action of the reagents on cell attachment. These results demonstrate a new functional activity of Der p1 that may be germane to the processes of allergen presentation, inflammatory cell activation, and chronic tissue injury.

The climate is a forced and dissipative nonlinear system featuring nontrivial dynamics on a vast range of spatial and temporal scales. The understanding of the climate's structural and multiscale properties is crucial for the provision of a unifying picture of its dynamics and for the implementation of accurate and efficient numerical models. We present some recent developments at the intersection between climate science, mathematics, and physics, which may prove fruitful in the direction of constructing a more comprehensive account of climate dynamics. We describe the Nambu formulation of fluid dynamics and the potential of such a theory for constructing sophisticated numerical models of geophysical fluids. Then, we focus on the statistical mechanics of quasi-equilibrium flows in a rotating environment, which seems crucial for constructing a robust theory of geophysical turbulence. We then discuss ideas and methods suited for approaching directly the nonequilibrium nature of the climate system. First, we describe some recent findings on the thermodynamics of climate, characterize its energy and entropy budgets, and discuss related methods for intercomparing climate models and for studying tipping points. These ideas can also create a common ground between geophysics and astrophysics by suggesting general tools for studying exoplanetary atmospheres. We conclude by focusing on nonequilibrium statistical mechanics, which allows for a unified framing of problems as different as the climate response to forcings, the effect of altering the boundary conditions or the coupling between geophysical flows, and the derivation of parametrizations for numerical models.

Receptor tyrosine kinases (RTK) are targets for anticancer drug development. To date, only RTK inhibitors that block orthosteric binding of ligands and substrates have been developed. Here, we report the pharmacologic characterization of the chemical SSR128129E (SSR), which inhibits fibroblast growth factor receptor (FGFR) signaling by binding to the extracellular FGFR domain without affecting orthosteric FGF binding. SSR exhibits allosteric properties, including probe dependence, signaling bias, and ceiling effects. Inhibition by SSR is highly conserved throughout the animal kingdom. Oral delivery of SSR inhibits arthritis and tumors that are relatively refractory to anti-vascular endothelial growth factor receptor-2 antibodies. Thus, orally-active extracellularly acting small-molecule modulators of RTKs with allosteric properties can be developed and may offer opportunities to improve anticancer treatment.

We present a model for the scaling of mixing in weakly rotating stratified flows characterized by their Rossby, Froude and Reynolds numbers Ro, F r, Re. It is based on quasiequipartition between kinetic and potential modes, sub-dominant vertical velocity w, and lessening of the energy transfer to small scales as measured by a dissipation efficiency β = V / D , with V the kinetic energy dissipation and D = u 3 rms /L int its dimensional expression, w, u rms the vertical and rms velocities, and L int the integral scale. We determine the domains of validity of such laws for a large numerical study of the unforced Boussinesq equations mostly on grids of 1024 3 points, with Ro/F r 2.5, and with 1600 Re ≈ 5.4 × 10 4 ; the Prandtl number is one, initial conditions are either isotropic and at large scale for the velocity, and zero for the temperature θ, or in geostrophic balance. Three regimes in Froude number, as for stratified flows, are observed: dominant waves, eddy-wave interactions and strong turbulence. A wave-turbulence balance for the transfer time τ tr = N τ 2 N L , with τ N L = L int /u rms the turn-over time and N the Brunt-Väisälä frequency, leads to β growing linearly with F r in the intermediate regime, with a saturation at β ≈ 0.3 or more, depending on initial conditions for larger Froude numbers. The Ellison scale is also found to scale linearly with F r. The flux Richardson number, with B f = N wθ the buoyancy flux, transitions for roughly the same parameter values as for β. These regimes for the present study are delimited bythe mixing efficiency, putting together the three relationships of the model allows for the prediction of the scaling Γ f ∼ F r −2 ∼ R −1 B in the low and intermediate regimes for high Re, whereas for higher Froude numbers, Γ f ∼ R −1/2 B, a scaling already found in observations: as turbulence strengthens, β ∼ 1, w ≈ u rms , and smaller buoyancy fluxes altogether correspond to a decoupling of velocity and temperature fluctuations, the latter becoming passive.